Human neonatal Fc receptor antibodies and methods of use thereof
View Patent ↗The disclosure relates to antibodies that bind FcRn and methods of using these antibodies.
1. An isolated antibody comprising a light chain variable region (V L ), a heavy chain variable region (V H ), and a heavy chain constant region (C H ), wherein the antibody binds to human neonatal Fc receptor (FcRn); and wherein
the V L comprises:
(i) a V L CDR1 comprising the amino acid sequence TGTGSDVGSYNLVS (SEQ ID NO:14);
(ii) a V L CDR2 comprising the amino acid sequence GDSQRPS (SEQ ID NO:15); and
(iii) a V L CDR3 comprising the amino acid sequence SSYAGSGIYV (SEQ ID NO:12) or ASYAGSGIYV (SEQ ID NO:13); and
the V H comprises:
(i) a V H CDR1 comprising the amino acid sequence EYAMG (SEQ ID NO:22);
(ii) a V H CDR2 comprising the amino acid sequence SIGSSGGQTKYADSVKG (SEQ ID NO:23); and
(iii) a V H CDR3 comprising the amino acid sequence LAIGDSY (SEQ ID NO:24); and
the C H has a deletion corresponding to the C-terminal lysine residue at the last position of SEQ ID NO:17.
2. The isolated antibody of claim 1 , wherein the V L of the isolated antibody comprises the amino acid sequence of SEQ ID NO: 8, SEQ ID NO: 10 or SEQ ID NO: 11.
3. The antibody of claim 1 , wherein the antibody binds human FcRn with a dissociation constant (K D ) of less than 10 nM.
4. The antibody of claim 1 , wherein the antibody is a human or humanized antibody or is non-immunogenic in a human.
5. The antibody of claim 1 , wherein the antibody is chimeric.
6. The antibody of claim 1 , wherein the antibody is selected from the group consisting of Fab, F(ab)′2, Fv, and scFv.
7. A pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier.
8. An isolated nucleic acid comprising a sequence that encodes the antibody of claim 1 .
9. A vector comprising the nucleic acid of claim 8 .
10. An isolated host cell comprising the vector of claim 9 .
11. A method of detecting FcRn in a sample, the method comprising:
(a) contacting the sample with the antibody of claim 1 , and
(b) detecting an interaction between the antibody and FcRn if present.
12. A method of detecting FcRn in a subject, the method comprising:
(a) administering to the subject the antibody of claim 1 , and
(b) detecting an interaction between the antibody and FcRn if present.
13. A method of modulating FcRn activity, the method comprising contacting FcRn with an effective amount the antibody of claim 1 , thereby modulating the activity of FcRn.
14. A method of treating an autoimmune disorder in a subject, the method comprising
administering to the subject the antibody of claim 1 in an amount sufficient to treat the autoimmune disorder.
15. A method of modulating the half-life and/or levels of circulating IgG in a subject, the method comprising
administering to the subject the antibody of claim 1 in an amount effective to modulate the half-life and/or levels of circulating IgG in the subject.
16. A method of modulating FcRn activity, the method comprising contacting FcRn with the antibody of claim 1 , thereby modulating the activity of FcRn.
17. A method of modulating the half-life and/or levels of circulating IgG in a subject, the method comprising
administering to the subject the antibody of claim 1 in an amount effective to modulate the half-life and/or levels of circulating IgG in the subject.